Epanova

Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Monitoring: Laboratory Tests

In some patients, EPANOVA increases LDL-C levels. LDL-C levels should be monitored periodically during therapy with EPANOVA.

In patients with hepatic impairment, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels should be monitored periodically during therapy with EPANOVA.

Fish Allergy

EPANOVA contains polyunsaturated free fatty acids derived from fish oils. It is not known whether patients with allergies to fish and/or shellfish, are at increased risk of an allergic reaction to EPANOVA. EPANOVA should be used with caution in patients with known hypersensitivity to fish and/or shellfish.

Patient Counseling Information

EPANOVA should be used with caution in patients with known sensitivity or allergy to fish and/or shellfish [see WARNINGS AND PRECAUTIONS].

Patients should be advised that use of lipid-regulating agents does not reduce the importance of adhering to diet [see DOSAGE AND ADMINISTRATION].

Patients should be advised not to alter EPANOVA capsules in any way and to ingest intact capsules only [see DOSAGE AND ADMINISTRATION].

Instruct patients to take EPANOVA as prescribed. If a dose is missed, patients should take it as soon as they remember. However if they miss one day of EPANOVA, they should not double the dose when they resume taking it.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

In a Sprague-Dawley rat carcinogenicity study with oral gavage doses of 100, 600, and 2,000 mg/kg/day omega-3 carboxylic acid, males were treated for 84 to 95 weeks without an increased incidence of tumors. In female rats treated for 66 to 95 weeks at 2000 mg/kg/day, an increased incidence of benign ovarian sex cord stromal tumors were observed (up to 5 times human systemic exposure following an oral dose of 4 grams/day based on a body surface area comparison). In a 6-month carcinogenicity study, Tg.rasH2 transgenic mice were treated with oral gavage doses of 500, 1000, 2000, and 4000 mg/kg/day omega-3 carboxylic acid without any increase in the incidence of tumors.

EPANOVA was not mutagenic or clastogenic with or without metabolic activation in the bacterial mutagenesis (Ames) test with Salmonella typhimurium and Escherichia coli or in the chromosomal aberration assay in Chinese hamster ovary cells. EPANOVA was negative in the in vivo rat bone marrow micronucleus assay.

In a rat fertility study with oral gavage doses of 100, 600, and 2,000 mg/kg/day, males were treated from 4 weeks prior to mating, and females were treated for 2 weeks prior to and throughout mating until day 6 of gestation. No adverse effect on male or female fertility was observed at 2,000 mg/kg/day (5 times human systemic exposure following an oral dose of 4 grams/day based on a body surface area comparison).

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. It is unknown whether EPANOVA can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. EPANOVA should be used during pregnancy only if the potential benefit to the patient justifies the potential risk to the fetus.

In female rats given oral gavage doses of 100, 600, and 2,000 mg/kg/day beginning 2 weeks prior to mating and continuing through day 6 of gestation, no adverse effects were observed in the high-dose group (5 times human systemic exposure following an oral dose of 4 grams/day based on body surface area comparison).

In pregnant rats given oral gavage doses of 100, 600, and 2,000 mg/kg/day from gestation day 6 through organogenesis , late embryonic deaths and embryos with skeletal variations were observed (5 times human systemic exposure following an oral dose of 4 grams/day based on a body surface area comparison).

In pregnant rabbits given oral gavage doses of 100, 500, and 750 mg/kg/day from gestation day 6 through organogenesis, skeletal malformations, variations in ossification, and visceral variations were observed in the fetuses in groups given up to 500 mg/kg/day (2 times human systemic exposure following an oral dose of 4 grams/day based on a body surface area comparison). At 750 mg/kg/day, several rabbits aborted and evidence of maternal toxicity was observed, and there was an increase in the incidence of fetuses with malformations and variations (4 times human systemic exposure following an oral dose of 4 grams/day based on a body surface area comparison).

In a multigenerational developmental study in pregnant rats given oral gavage doses of 100, 600, and 2,000 mg/kg/day from gestation day 6 through lactation day 21, difficulties during and shortly after parturition led to morbidity/mortality in 9 of 24 dams given the highest dose (5 times human systemic exposure following an oral dose of 4 grams/day based on a body surface area comparison). There were no abnormalities observed in offspring (F1) from treated dams. However, survival was decreased from day 10 of lactation onward in second generation offspring (F2) from dams given 600 mg/kg/day (1.5 times the human systemic exposure following an oral dose of 4 grams/day based on a body surface area comparison).

Labor And Delivery

There are no human studies that have investigated the effects of EPANOVA on preterm labor or labor at term. However, animal studies showed that omega-3 fatty acids caused delayed parturition and associated fetal death in rats (5 times the human systemic exposure following an oral dose of 4 g/day based on body surface area comparison), and premature birth and abortion in rabbits (4 times human systemic exposure following an oral dose of 4 grams/day based on a body surface area comparison).

Nursing Mothers

Studies with omega-3 fatty acids derived from fish oil have demonstrated excretion in human milk at levels higher than that in plasma. The effect of this excretion on the infant of a nursing mother is unknown; caution should be exercised when EPANOVA is administered to a nursing mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been studied.

Geriatric Use

Clinical studies of EPANOVA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Last reviewed on RxList: 5/20/2014
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions
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